Background: Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) infection resembles a multisystemic hyperinflammatory syndrome that involves the complement cascade. Complement activation however appears to spare FCoV-infected cells and therefore does not effectively contribute to virus clearance. Hypotheses/
Objectives: To evaluate whether FCoV-infected cells are protected by autocrine/paracrine expression of complement-regulating factors. Animals/Tissues: The study enrolled postmortem tissues of 31 cats with PCR/IHC-confirmed FIP.
Methods: Sections of formalin-fixed, paraffin-embedded tissue from FIP lesions underwent immunohistochemical double-staining for (1) FCoV antigen plus (2a) complement-regulating factors (CRF) CD46 and CD59 as well as (2b) complement factors C1q and C9. Marker expression was scored semiquantitatively and their spatial relationship was statistically evaluated.
Results: All 31 cats presented with FCoV-positive foci, of which a majority co-expressed both CRFs CD46 and CD59 (p< 0.05) albeit to a variable extent. C1q and C9 were not seen in or next to FCoV-positive cells. Moreover, the higher the CRF expression, the larger was the distance to C1q- and C9-positive lesions (p< 0.05). Conclusions & Clinical Relevance: Complement-regulating factors indeed seem to protect FCoV-infected cells from complement-mediated cytolysis and virus clearance. Likewise, CRFs suppress activation of C1 complex that initiates early cleavage cascades of the classical pathway as much as they suppress C9 polymerization and formation of the membrane attack complex. No such suppression is seen in prototypic FIP lesions distant to infected cells, where complement activation contributes to tissue damage.
